Bezuclastinib + Sunitinib for GIST

Recruiting in Palo Alto (17 mi)

+3 other locations

Overseen by Candace Haddox, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Sarcoma Alliance for Research through Collaboration

Must be taking: Sunitinib

Must not be taking: Strong CYP3A4 inhibitors

Disqualifiers: HIV, Cardiac disease, others

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is an open label, single arm, phase 2 trial investigating bezuclastinib plus sunitinib in patients with GIST who have previously progressed on sunitinib.

Will I have to stop taking my current medications?

The trial requires that you stop taking any strong CYP3A4 inhibitors or inducers at least 14 days before starting the study drug. If you are on any anticancer drugs, you must stop them at least 5 half-lives or 14 days before the trial, whichever is shorter. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug Bezuclastinib + Sunitinib for GIST?

Research shows that Sunitinib, one of the drugs in the treatment, is effective for patients with gastrointestinal stromal tumors (GIST) who no longer respond to another drug called imatinib. It has been shown to help manage the disease and is considered a key part of therapy for advanced GIST.

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Is the combination of Bezuclastinib and Sunitinib safe for humans?

Sunitinib, used for treating gastrointestinal stromal tumors (GIST), can cause severe side effects that sometimes lead to stopping the treatment. It's important to monitor for these side effects to ensure patients can safely continue the therapy.

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How is the drug Bezuclastinib + Sunitinib unique for treating GIST?

The combination of Bezuclastinib and Sunitinib for treating gastrointestinal stromal tumors (GIST) is unique because Sunitinib is a multitargeted tyrosine kinase inhibitor that is effective for GIST after failure of Imatinib, and Bezuclastinib may offer additional benefits by targeting different pathways or mutations that cause resistance to Sunitinib.

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Eligibility Criteria

This trial is for patients with Gastrointestinal Stromal Tumors (GIST) who have already tried sunitinib but their disease has progressed. Specific eligibility details are not provided, so interested individuals should inquire further to determine if they meet the inclusion and exclusion criteria.

Inclusion Criteria

Life expectancy of > 12 weeks

I had hepatitis C but have been treated and cured.

My scans show at least one area of cancer that can be measured.

Exclusion Criteria

I haven't had major surgery in the last 4 weeks or I've fully recovered from recent surgery.

Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen may be included after discussion with the Principal Investigator

I have previously been treated with bezuclastinib.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Washout

Patients undergo a washout period before starting treatment

2 weeks

Treatment

Participants receive bezuclastinib and add sunitinib 2 weeks later, continuing until progression, unacceptable toxicity, or withdrawal of consent

Up to 2 years

Imaging response assessments every 8 weeks until 15 months, then every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Participant Groups

The study is testing a combination of two drugs: Bezuclastinib and Sunitinib, in people with GIST. It's an open-label, single-arm phase II trial, meaning all participants will receive the same treatment without a comparison group or placebo.

Group I: bezuclastinib in combination with sunitinib Experimental Treatment 1 Intervention

Bezuclastinib 600 mg (tablet) administered orally daily Sunitinib 37.5 mg administered orally daily Patients will begin bezuclastinib and add sunitinib 2 weeks later. Each cycle is 28 days.

Sunitinib is already approved in United States, European Union, Canada, Japan for the following indications:

🇺🇸 Approved in United States as Sutent for:

• Renal Cell Carcinoma
• Gastrointestinal Stromal Tumor

🇪🇺 Approved in European Union as Sutent for:

• Renal Cell Carcinoma
• Gastrointestinal Stromal Tumor
• Pancreatic Neuroendocrine Tumors

🇨🇦 Approved in Canada as Sutent for:

• Renal Cell Carcinoma
• Gastrointestinal Stromal Tumor

🇯🇵 Approved in Japan as Sutent for:

• Renal Cell Carcinoma
• Gastrointestinal Stromal Tumor

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Sylvester Comprehensive Cancer Center, University of Miami Miami, FL

Fox Chase Cancer Center Philadelphia, PA

Dana Farber Cancer Institute Boston, MA

Oregon Health & Science University Portland, OR

Who Is Running the Clinical Trial?

Sarcoma Alliance for Research through Collaboration Lead Sponsor

Cogent Biosciences, Inc. Industry Sponsor

The Life Raft Group Collaborator

Dana-Farber Cancer Institute Collaborator

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Sunitinib malate for gastrointestinal stromal tumour in imatinib mesylate-resistant patients: recommendations and evidence. [2021] Is sunitinib malate-marketed as Sutent (Pfizer Canada, Kirkland, QC)-superior to placebo or other interventions for primary outcomes of interest in adult patients with gastrointestinal stromal tumour (GIST) who have developed resistance or who exhibit intolerance to imatinib mesylate (IM)?

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of sunitinib in Chinese patients with imatinib-resistant or -intolerant gastrointestinal stromal tumors. [2022] To assess the efficacy and safety of sunitinib in Chinese patients with imatinib-resistant or -intolerant gastrointestinal stromal tumors (GISTs), and evaluate the impact of genotype on sunitinib efficacy.

3. United States pubmed.ncbi.nlm.nih.gov

Sunitinib, a multitargeted tyrosine kinase inhibitor, in the management of gastrointestinal stromal tumor. [2019] Due to the remarkable advances in the understanding of the biology of gastrointestinal stromal tumors (GIST), tyrosine kinase inhibition has become the mainstay of therapy for patients with advanced GIST. Sunitinib is a tyrosine kinase inhibitor with a wide range of kinase inhibition, including KIT, platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor (VEGF), and FLT3. Sunitinib has demonstrated benefit in patients with advanced GIST who have progressed on primary therapy with imatinib. The objectives of this review are to discuss the role of sunitinib in the current management of GIST, to review the unique side effect profile of the agent, and to discuss future trends in the use of the drug as the understanding of the mechanism of GIST evolves.

4. United States pubmed.ncbi.nlm.nih.gov

Clinical outcomes of patients with advanced gastrointestinal stromal tumors: safety and efficacy in a worldwide treatment-use trial of sunitinib. [2022] The objectives of this study were to provide sunitinib to patients with gastrointestinal stromal tumor (GIST) who were otherwise unable to obtain it and to collect broad safety and efficacy data from a large population of patients with advanced GIST after imatinib failure. (ClinicalTrials.gov identifier NCT00094029).

5. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of sunitinib on patients with imatinib-resistant gastrointestinal stromal tumor]. [2022] To investigate the efficacy and safety of sunitinib on the management of gastrointestinal stromal tumors (GIST) patients with imatinib resistance.

6. England pubmed.ncbi.nlm.nih.gov

Tyrosine kinase inhibition in renal cell carcinoma and gastrointestinal stromal tumours: case reports. [2020] Sunitinib malate is approved multinationally for the treatment of metastatic renal cell carcinoma (mRCC) and advanced imatinib-refractory gastrointestinal stromal tumour (GIST). Greater exposure to sunitinib is associated with improved efficacy. Therefore, minimising the impact of adverse events (AEs) on patient quality of life is important to enable patients to achieve optimal exposure to sunitinib and maximum clinical benefit.

7. England pubmed.ncbi.nlm.nih.gov

Sunitinib therapy for imatinib-resistant and/or intolerant gastrointestinal stromal tumors: comparison of safety and efficacy between standard and reduced dosage regimens. [2023] Sunitinib therapy for patients with imatinib-resistant and/or intolerant gastrointestinal stromal tumors (GISTs) often causes severe adverse events (AEs) that lead to treatment discontinuation.

8. Japan pubmed.ncbi.nlm.nih.gov

[Strategy for patients with GIST after failure of imatinib]. [2015] Sunitinib malate(SU11248)is an oral multitargeted receptor tyrosine kinase inhibitor(MTI)that has antitumor activities for patients with gastrointestinal stromal tumor; GIST after failure of Imatinib. Sunitinib has demonstrated significant clinical benefits, including PFS, RR and OS in the USA and Japan. However, cis-mutations in the activation loop of the KIT gene tend to develop Sunitinib-resistant GIST. Two clinical trials revealed that new multitargeted receptor tyrosine kinase inhibitors, Sorafenib and Nilotinib, had antitumor activities for Sunitinib-resistant GIST with longer PFS and a different spectrum. Now, clinical trials of several new MTIs are ongoing in Western countries. Inhibition of the KIT gene cis-mutations and antiangiogenesis activities may be essential for the strategy for Imatinib/Sunitinibresistant GIST.

9. United States pubmed.ncbi.nlm.nih.gov

Approval summary: sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma. [2022] To describe the Food and Drug Administration (FDA) review and approval of sunitinib malate (Sutent). Sunitinib received regular approval for the treatment of gastrointestinal stromal tumor (GIST) after disease progression or intolerance to imatinib mesylate (Gleevec). Additionally, sunitinib received accelerated approval for the treatment of advanced renal cell carcinoma.

10. England pubmed.ncbi.nlm.nih.gov

The potential of sunitinib as a therapy in ovarian cancer. [2018] Sunitinib malate (SU11248; Sutent®; Pfizer, Inc., New York) is a multi-kinase inhibitor currently approved for use in advanced renal cell carcinoma (RCC), imatinib-resistant/-intolerant gastrointestinal stromal tumours and progressive, well-differentiated pancreatic neuroendocrine tumours in patients with unresectable, locally advanced or metastatic disease.

11. England pubmed.ncbi.nlm.nih.gov

Molecular basis for sunitinib efficacy and future clinical development. [2022] Sunitinib malate (SU11248/Sutent; Pfizer) is a multitargeted tyrosine kinase inhibitor that has potent anti-angiogenic and antitumour activities. Definitive efficacy has been demonstrated in advanced renal cell carcinoma and in gastrointestinal stromal tumours that are refractory or intolerant to imatinib (Gleevec; Novartis), which has provided the basis for the recent regulatory approvals for these indications. This article summarizes the discovery and development of sunitinib, and discusses key issues for the multitargeted approach in cancer treatment, such as markers of response and development of resistance, and their significance for the future development of sunitinib and other multikinase inhibitors.